Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review

2021 ◽  
Vol 41 (3) ◽  
pp. 261-272
Author(s):  
Chau Wei Ling ◽  
Kamal Sud ◽  
Connie Van ◽  
Syed Tabish Razi Zaidi ◽  
Rahul P. Patel ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Case Reports ◽  
Plasma Concentrations ◽  
Case Series ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
Automated Peritoneal Dialysis ◽  
Final Study ◽  
Drug Plasma

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.

scholarly journals Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis

2016 ◽  
Vol 60 (6) ◽  
pp. 3558-3562 ◽  
Author(s):  
Hongfei Zhang ◽  
M. Hong Nguyen ◽  
Cornelius J. Clancy ◽  
Rujuta Joshi ◽  
Wenchen Zhao ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Transplant ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Treatment Strategies ◽  
Area Under The Curve ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
Average Dose

Invasive fungal infections (IFIs) are common among lung transplant recipients (LTRs). Posaconazole is an important antifungal agent for both prophylaxis and treatment of IFIs; however, detailed pharmacokinetic data are limited among LTRs, particularly those with cystic fibrosis (CF). Our objective was to conduct a pharmacokinetic study of posaconazole oral suspension among LTRs, with particular attention to patients with CF. We enrolled 20 LTRs, 7 with CF and 13 with other underlying lung diseases. Average daily doses in CF and non-CF patients were 829 and 862 mg, respectively. After ≥5 days of treatment, only 4 patients had average plasma concentrations of >0.7 μg/ml. Average steady-state plasma concentrations were 61% lower in CF patients (0.233 μg/ml) than in non-CF LTRs (0.594 μg/ml;P= 0.03). The average dose-normalized plasma area-under-the-curve (AUC) values were also lower in CF (0.007 h·μg/ml) than in non-CF LTRs (0.02 h·μg/ml;P= 0.02). The weight-normalized apparent oral clearance values were 2.51 and 0.74 liters/h/kg among CF and non-CF LTRs, respectively (P= 0.005). Despite significant interpatient variability, plasma trough concentrations were strongly correlated with posaconazole AUC across all LTRs (r2= 0.95,P< 0.0001). Taken together, our study highlights a critical need to incorporate new formulations of posaconazole into prophylaxis and treatment strategies for LTRs, particularly those with CF. Future pharmacokinetic studies of both tablet and intravenous formulations must consider LTR-specific factors and incorporate a therapeutic drug monitoring plan in this patient population.

scholarly journals Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Josée Bouchard ◽  
Greene Shepherd ◽  
Robert S. Hoffman ◽  
Sophie Gosselin ◽  
Darren M. Roberts ◽  
...  
Keyword(s):  
Kidney Function ◽  
Case Reports ◽  
Torsade De Pointes ◽  
Case Series ◽  
Clinical Analysis ◽  
Intermittent Hemodialysis ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
Adrenergic Antagonists

Abstract Background β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning. Methods We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. Results A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations. Conclusions BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.

scholarly journals Prophylaxis of Invasive Fungal Infections: A Review of the Use of Posaconazole

2009 ◽  
Vol 1 ◽  
pp. CMT.S1948
Author(s):  
Curtis D. Collins ◽  
Jeannina A. Smith ◽  
Daniel R. Kaul
Keyword(s):  
At Risk ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Case Reports ◽  
Case Series ◽  
Individual Case ◽  
Invasive Fungal Infections ◽  
Cost Of Care ◽  
Therapeutic Drug ◽  
Patients At Risk

Invasive fungal infections (IFIs) cause significant morbidity, mortality, and increased cost of care in patients with hematological malignancies, prolonged (i.e. >7-10 days) treatment induced neutropenia, and other disease states causing underlying immunosuppression. One strategy often used to combat the development of invasive infections is the use of antifungal agents as prophylaxis in at risk patients. Posaconazole is an oral triazole with a useful spectrum of activity against many fungal pathogens of concern in patients at risk for the development of IFIs. Posaconazole is only available in oral formulation and therapeutic drug monitoring may provide value due to variable absorption and serum concentrations. Clinical efficacy and pharmacoeconomic data have demonstrated the utility of posaconazole in the treatment of oropharyngeal candidiasis and for prophylaxis in patients at risk for development of IFIs. Several organizations or expert groups involved in developing guidelines for the management of IFIs recommend posaconazole anti-fungal prophylaxis in patients with AML or MDS and chemotherapy induced neutropenia or significant GVHD. In addition, nonrandomized studies (largely of salvage therapy) and case series suggest that posaconazole may be effective as treatment for invasive aspergillosis, zygomycosis, and coccidiomycosis. Further, small case series or individual case reports suggest activity against other less commonly encountered filamentous fungi and Histoplasma.

Plasma concentrations resulting from continuous infusion of meropenem in a community-based outpatient program: A case series

2020 ◽  
Vol 77 (24) ◽  
pp. 2074-2080
Author(s):  
Amy Legg ◽  
Melanie Halford ◽  
Kate McCarthy
Keyword(s):  
Continuous Infusion ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Case Series ◽  
Infectious Complications ◽  
Antimicrobial Treatment ◽  
Therapeutic Drug ◽  
Community Based ◽  
Drug Concentrations ◽  
Tertiary Center

Abstract Purpose Traditionally meropenem has been considered too unstable in solution for continuous infusion. However, in the era of increasing antimicrobial resistance, use of meropenem is becoming more frequently required, and the ability to facilitate its administration via community-based programs would be beneficial. There are some reassuring data about meropenem stability in solution, but data about actual drug exposure in patients and subsequent clinical outcomes are lacking. Summary Here we present a case series of 4 patients at a single tertiary center who received meropenem via continuous infusion coordinated through an outpatient parenteral antimicrobial treatment (OPAT) program. We provide plasma drug concentrations achieved and report on the patients’ clinical progress. All patients achieved drug concentrations of at least 2 times the minimum inhibitory concentration (MIC) while receiving meropenem via continuous infusion and had resolution of their infectious complications. No adverse effects of meropenem continuous infusion were noted. Conclusion Meropenem continuous infusion along with therapeutic drug monitoring was used successfully in a community-based program. Due to interpatient pharmacokinetic variability, we consider meropenem concentration monitoring compulsory during continuous-infusion meropenem therapy.

scholarly journals Computed tomography of the heads of ancient Egyptian mummies: a systematic review of the medical literature.

NEMESIS ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 1-49
Author(s):  
Raphael Olszewski ◽  
Jean-Philippe Hastir ◽  
Caroline Tilleux ◽  
Luc Delvaux ◽  
Etienne Danse
Keyword(s):  
Systematic Review ◽  
Current Knowledge ◽  
Case Reports ◽  
Case Series ◽  
Ct Scanning ◽  
General Information ◽  
Exclusion Criteria ◽  
Ancient Egyptian ◽  
Final Study

Objective: To summarize the current knowledge on CT scanning of Egyptian mummy heads and faces and provide more valid methodology than that previously available. Material and methods: A systematic review was performed by one observer using two biomedical databases: PubMed and EMBASE. Inclusion and exclusion criteria were applied along with language restrictions. Finally, 2120 articles were found, 359 articles were duplicated among all search equations, 1454 articles were excluded, 307 articles were retained for full review, and 28 articles (31 mummies) were selected for the final study (PRISMA workflow). Results: The data were categorized into the following groups: 1) general information; 2) 1st author affiliation; 3) CT radiological protocol; 4) excerebration pathways; 5) soft tissue preservation; 6) dental status and displaced teeth; 7) packing of the mouth, ears, nose, and eyes, and 8) outer facial appearance. The evidence-based quality of the studies was low because only case reports and small case series were found. Discussion: The embalming art applied to a mummified head and face shows great variability across the whole span of Egyptian civilization. The differences among the various embalming techniques rely on multiple tiny details that are revealed by meticulous analysis of CT scans by a multidisciplinary team of experts. Conclusion: There is a need for more systematization of the CT radiological protocol and the description of Egyptian mumm’y heads and faces to better understand the details of embalming methods.  

scholarly journals Vancomycin in peritoneal dialysis: Clinical pharmacology considerations in therapy

2020 ◽  
Vol 40 (4) ◽  
pp. 384-393
Author(s):  
Edwin Lam ◽  
Yi Ting (Kayla) Lien ◽  
Water K Kraft ◽  
Beth Piraino ◽  
Valvanera Vozmediano ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Pharmacokinetic Data ◽  
Automated Peritoneal Dialysis ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Optimal Dosing ◽  
Dosing Algorithm

Intraperitoneal vancomycin is the first-line therapy in the management of peritoneal dialysis (PD)-related peritonitis. However, due to the paucity of data, vancomycin dosing for peritonitis in patients on automated peritoneal dialysis (APD) is empiric and based on clinical experience rather than evidence. Studies in continuous ambulatory peritoneal dialysis (CAPD) patients have been used to provide guidelines for dosing and are often extrapolated for APD use, but it is unclear whether this is appropriate. This review summarizes the available pharmacokinetic data used to inform optimal dosing in patients on CAPD or APD. The determinants of vancomycin disposition and pharmacodynamic effects are critically summarized, knowledge gaps explored, and a vancomycin dosing algorithm in PD patients is proposed.

Pyrazinamide and Rifampicin Regimens for Patients on Maintenance Dialysis

1988 ◽  
Vol 11 (3) ◽  
pp. 181-185 ◽  
Author(s):  
J. Woo ◽  
A. Leung ◽  
K. Chan ◽  
K.N. Lai ◽  
R. Teoh
Keyword(s):  
Renal Failure ◽  
Peritoneal Dialysis ◽  
Plasma Concentrations ◽  
Pharmacokinetic Studies ◽  
Bactericidal Action ◽  
Dialysis Treatment ◽  
End Stage Renal Failure ◽  
Maintenance Dialysis ◽  
End Stage ◽  
Higher Doses

We measured pyrazinamide and rifampicin plasma concentrations in five patients with pulmonary tuberculosis and end stage renal failure treated by haemodialysis or continuous ambulatory peritoneal dialysis. Using conventional daily doses of oral pyrazinamide and rifampicin, we found that the drugs were removed efficiently by both dialysis methods, so that plasma levels were sub-optimal for maximal bactericidal action. These findings suggest that in patients with tuberculosis on maintenance dialysis, treatment should be either with higher doses of these two drugs, or with additional replacement doses given after each dialysis. Further detailed pharmacokinetic studies on larger numbers of patients are indicated.

scholarly journals Lithium Medication in Pregnancy and Breastfeeding—A Case Series

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 634
Author(s):  
Andrea Gehrmann ◽  
Katrin Fiedler ◽  
Anna Linda Leutritz ◽  
Carolin Koreny ◽  
Sarah Kittel-Schneider
Keyword(s):  
Case Reports ◽  
Lithium Treatment ◽  
Case Series ◽  
Mood Stabilizers ◽  
Lithium Salts ◽  
Therapeutic Drug ◽  
Cardiac Malformation ◽  
First Line ◽  
Teratogenic Risk ◽  
Healthy Infants

Lithium salts are the first-line prophylaxis treatment for bipolar disorder in most guidelines. The majority of bipolar women are treated with mood stabilizers at the time they wish to get pregnant. One reason for this is the rising average age at first childbirth, at least in the high-income countries, which increases in general the likelihood of a medication with psychotropic drugs. Previously, lithium exposition during pregnancy was thought to strongly increase the risk of severe cardiac malformation. However, recent studies only point to a low teratogenic risk, so nowadays an increasing number of women are getting pregnant with ongoing lithium treatment. Regarding lithium medication during breastfeeding, there is evidence that lithium transfers to the breastmilk and can also be detected in the infants’ serum. The influence on the infant is still a largely understudied topic. Regular monitoring of the infants’ renal clearance, thyroid function, and lithium levels is warranted when breastfeeding under lithium exposure. In this case series, we present three case reports of bipolar mothers who were treated with lithium during pregnancy and breastfeeding to add to the scarce literature on this important topic. In short, we strengthen the importance of therapeutic drug monitoring due to fluctuating plasma levels during pregnancy and after birth, and we can report the birth and development of three healthy infants despite lithium medication during pregnancy and breastfeeding.

scholarly journals The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants

2005 ◽  
Vol 7 (3) ◽  
pp. 231-247 ◽  
Keyword(s):  
Clinical Laboratory ◽  
Psychiatric Patients ◽  
Plasma Concentrations ◽  
Clinical Effectiveness ◽  
Drug Analysis ◽  
Therapeutic Monitoring ◽  
Patient Treatment ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Consensus Guidelines

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration-clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM. Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants.

scholarly journals 1111. Therapeutic Drug Monitoring of Colistin in Cerebrospinal Fluid in the Treatment of Neurosurgical Meningitis caused by Pseudomonas aeruginosa and KPC-producing Enterobacterales

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S647-S647
Author(s):  
Mohamad Yasmin ◽  
Amir nutman ◽  
Steven Marshall ◽  
Lu Wang ◽  
Ke Chen ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
External Ventricular Drain ◽  
Plasma Concentrations ◽  
Cns Infection ◽  
Therapeutic Drug ◽  
Pharmacokinetic Data ◽  
Research Support ◽  
Cns Infections

Abstract Background Central nervous system (CNS) infections caused by carbapenem-resistant Enterobacterales (CRE) and Difficult-to-treat resistant (DTR)-P. aeruginosa (PA) present a therapeutic dilemma. Therapies are limited due to antibiotic resistance and inadequate CNS diffusion. Intraventricular polymyxins are utilized in this setting despite a lack in pharmacokinetic data after CNS injection. We describe the utilization of intravenous and intrathecal polymyxin E [colistimethate (CMS)] therapeutic drug monitoring (TDM) in 3 cases of post-neurosurgical meningitis. Methods Bacterial identification and susceptibility testing were performed using MicroScan. TDM was employed by dosing CMS at 125,000 IU (i.e., 4.1 mg CBA or 10 mg) administered via external ventricular drain twice daily and 4.5 MIU (133.2 CBA or 360 mg) CMS administered over 30 minutes IV twice daily. Four pairs of CSF and blood samples were collected for each patient (Table 1). Samples were placed on ice to minimize in-vitro conversion of CMS to Colistin. Colistin binding in plasma and CSF was measured using ultracentrifugation. Concentrations of CMS and Colistin in CSF and human plasma were determined by liquid chromatography/mass spectrometry. Patients A, B and C received 20, 15, and 12 doses of CMS, respectively, prior to TDM. Results Bacterial cultures revealed DTR PA, blaKPCE. cloacae and blaOXA-48K. pneumoniae for patients A, B and C, respectively. Colistin minimum inhibitory concentrations (MIC) were 0.5 µg/ml, 0.125 µg/ml, and 0.125 µg/ml, respectively. The measured CSF and plasma concentrations of CMS, Colistin, and binding are shown in Table 1. Clinical resolution and microbiological cure were attained in all patients. Therapeutic Drug Monitoring of Unchanged CMS and Formed Colistin in CSF samples for patient A, B, and C Therapeutic Drug Monitoring of Unchanged CMS and Formed Colistin in Plasma Samples for patient A, B, and C Conclusion Favorable concentrations of formed Colistin and CMS in CSF were achieved in 3 patients with complicated CNS infection. To the best of our knowledge, this is the first study to report the binding of Colistin in CSF in humans. A TDM method was effectively applied to demonstrate that Colistin achieves and maintains the PK/PD target (fAUC/MIC) [ratio of area under the plasma concentration curve of unbound drug to MIC] that best correlates with killing activity. Overall, our results support intraventricular polymyxins for treating DTR Gram-negative CNS infections. Disclosures Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

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